Asparagine is a non-essential amino acid, and specifically is the beta amide of aspartic acid that exists in both the d(+) and 1(-) isomeric forms. It is widely distributed in plants and animals as it is found both in free form and as a component in proteins. The amino acid has useful applications as a flavor ingredient, and in medicine and biochemical research. Its chemical formula NH.sub.2 COCH.sub.2 CH(NH.sub.2)COOH renders it a white crystalline solid that is nearly insoluble in ethanol, methanol, ether and benzene while soluble in acids and alkalies.
L-asparagine synthesis is known by treating betamethyl-L-aspartate with an alcoholic solution of ammonia, see Beecham A. F., J. Am. Chem. Soc. 76, 4615 (1954). However, this treatment must be run for at least two days in order to obtain acceptable yields. Another article by Miller et. al entitled "The Synthesis of Glutamine and Asparagine Peptides and of Glutamine" teaches the amidation of carbobenzyloxy-L-glutamic acid-gamma-ethyl ester in aqueous ammonia followed by acidification to recover carbobenyoxy-L-glutamine Arch. Biochem. Biophys. 35 176-183 (1952).
U.S. Pat. No. 3,979,499 to Hirsbrunner et. al. discloses the chemical synthesis of asparagine or glutamine from beta-methyl aspartate hydrochloride. The beta methyl aspartate hydrochloride is typically first made by reacting aspartic acid with methanol and hydrochloric acid. See Gmeiner et. al., JOC 55 pp 3068-74. The intermediate is isolated through precipitation with an organic solvent and after the methanol is driven off is reacted with ammonia to yield the final asparagine product.
U.S. Pat. Nos. 2,798,092, 3,105,852 and 2,883,399 all disclose the synthesis of L-glutamine through the esterification and amidation of L-glutamic acid or its derivatives.
The present invention is directed to a novel process for the synthesis of L-asparagine which does away with a number of elements required by synthetic chemical routes known in the art. The absence of these elements enables the synthesis of the amino acid in a far less expensive and hazardous manner.